#5 PH 150A Jan29 H1N1 Pandemic (Reingold)

#5 PH 150A Jan29 H1N1 Pandemic (Reingold) - Infectious...

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Unformatted text preview: 2/10/2010 Infectious Disease Epidemiology: Where is It done? • Local and State Health Departments The 2009 H1N1 Influenza Pandemic: An Update Arthur L. Reingold, MD Professor, Division of Epidemiology Associate Dean for Research School of Public Health, University of California, Berkeley • CDC • Ministries of Health • International Agencies (e.g. WHO) • Academic Institutions (e.g. SPHs and Medical Schools) • Research Organizations • Health Care Provider Organizations (e.g. Kaiser) Infectious Disease Epidemiology: Content Areas • Descriptive Observational Epidemiologic Studies • Analytic Observational Epidemiologic Studies • Analytic Experimental Epidemiologic Studies (e.g. vaccine trials, clinical trials of treatment) • Mathematical Modelling Studies • Disease Surveillance • Outbreak Response/Investigation Response/Investigation 1 2/10/2010 INFLUENZA VIRUSES • 3 Types: A, B, C • Only Influenza A Viruses Cause Pandemics • Influenza A Surface Glycoproteins: Glycoproteins: • 16 hemagglutinins; 9 neuraminidases hemagglutinins; SELECTED SELECTED EPIDEMIOLOGIC FEATURES OF INFLUENZA • • • Incubation Period: 1-4 days (mean ~2 days) 1Serial Interval: 2-4 days 2Interval of Viral Shedding: 1-2 days before onset of before illness 4illness to 4-5 days after onset of illness in adults; peak shedding 1-2 days after onset 1Routes of Transmission: Large droplets (>5µm); near range aerosols; ? via fomites, hands, other surfaces fomites, Duration of “waves” in a community: ? 4 - 8 weeks • Nomenclature: • • Human: A/Victoria (H3N2) Animal: A/Chicken/Hong Kong/G9/97 [H9N2] • • • Mechanisms of Change: Drift and Shift CIRCUMSTANCES REQUIRED FOR AN INFLUENZA PANDEMIC 1. The influenza virus must be pathogenic in people. people. 2. The influenza virus must be readily transmissible from person to person. person. 3. The proportion of the population with protective antibodies must be low. Year INFLUENZA PANDEMICS SINCE 1847 Influenza A Subtype ? H2N? H1N1 (“Swine” or “Spanish”) H2N2 (“Asian”) H3N2 (“Hong Kong”) H1N1 (“Swine”) Estimated Mortality Worldwide ? ? ~40-50 million 1-2 million ~700,000 ? 1847 1889 1918 1957 1968 2009 USPHS STUDIES, 1918-9 & 1928-9 AGE-SPECIFIC CLINICAL MORBIDITY THE “W-SHAPED CURVE”: AGE-SPECIFIC MORTALITY (NO. DEATHS/PERSONS IN IN AGE RANGE) AGE-SPECIFIC MORTALITY, ADJUSTED FOR ATTACK RATE Figure from Taubenberger&Morens. Emerging Infectious Diseases 2006;12:15-22 2 2/10/2010 History of Reassortment Events in the Evolution of the 2009 Influenza A (H1N1) Virus Figure 1. History of Reassortment Events in the Evolution of the 2009 Influenza A (H1N1) Virus. The eight segments shown within each virus code for the following proteins of the influenza A virus (top to bottom): polymerase PB2, polymerase PB1, polymerase PA, hemagglutinin, nuclear protein, neuraminidase, matrix proteins, and nonstructural proteins. The segments of the human 2009 influenza A (H1N1) virus have coexisted in swine influenza A virus strains for more than 10 years. The ancestors of neuraminidase have not been observed for almost 20 years. The mixing vessel for the current reassortment is likely to be a swine host but remains unknown. Trifonov V et al. N Engl J Med 2009;361:115-119 3 2/10/2010 Age Distribution of 168 Critically Ill Patients With Confirmed or Probable 2009 Influenza A(H1N1) Kumar, A. et al. JAMA 2009;302:1872-1879. Copyright restrictions may apply. Age Distribution of 58 Critically Ill Patients With Confirmed, Probable, or Suspected 2009 Influenza A(H1N1) Infection Hospitalization and Fatality Rates and Case-Fatality Proportion Among Reported Hospitalized and Fatal Pandemic 2009 Influenza A(H1N1) Cases, by Age Group--California, April 23 Through August 11, 2009 Louie, J. K. et al. JAMA 2009;302:1896-1902. Dominguez-Cherit, G. et al. JAMA 2009;302:1880-1887. Copyright restrictions may apply. Copyright restrictions may apply. Comorbidities of Critically Ill Patients With Confirmed or Probable 2009 Influenza A(H1N1) Infection Histogram of Number of Concurrent Patients Receiving ECMO Across Australia and New Zealand in 2009 The Australia and New Zealand Extracorporeal Membrane Oxygenation (ANZ ECMO) Influenza Investigators, JAMA 2009;302:1888-1895. Kumar, A. et al. JAMA 2009;302:1872-1879. Copyright restrictions may apply. Copyright restrictions may apply. 4 2/10/2010 2009 H1N1 Influenza pandemic: Tentative Observations • Strain is new • Pre-existing immunity is non-existent or low; probably Prenonconfined to older age groups Younger • Younger age groups affected (compared with seasonal influenza) influenza) • Among those who are ill, older individuals and those with underlying conditions more likely to become severely ill/die • Currently sensitive to oseltamavir • Virus hasn’t yet evolved; circulating widely in northern and southern hemispheres 2009 H1N1 Influneza Pandemic: What we don’t know • Will a “second wave” occur? • Will the virus change? Become resistant to oseltamavir? oseltamavir? 5 2/10/2010 Projections concerning the possible burden on the U.S. Health care system • Possible burden on the U.S. Health Care System of an influenza pandemic, based on 1957 and 1968 pandemics: • 839,000 - 9,625,000 excess hospitalizations • 18 - 42 million excess outpatient visits • 20 - 47 million excess illnesses PANDEMIC INFLUENZA PREPAREDNESS: INFECTION CONTROL in the Health Care Setting • Focus is on preventing direct and indirect inoculation of the respiratory tract: tract: • Limit contact between infected and non-infected persons (e.g. isolation nonof patients; limiting contact with non-essential personnel and visitors) nonvisitors) Promote spatial separation common areas reas • Promote spatial separation in common areas • Use of contact and airborne precautions, including N95 respirators, when appropriate (e.g. aerosol-generating procedures) aerosol• Use of masks and cough etiquette/respiratory hygiene by symptomatic patients • Use of standard precautions for disposal of solid waste; linen and laundry; dishes; patient care equipment, and environmental cleaning) • Vaccination of health care workers Based on 1918 Pandemic: • • • • • 90 million cases 4.2 million outpatient visits 9.9 million hospitalizations 1.9 million deaths $255 billion in costs QUARANTINE AND ISOLATION • Quarantine is the separation and restriction of movement of apparently healthy people or animals who may have been exposed to a microbial threat and therefore may become infectious (DGMQ, 2004). CDC quarantine stations and many of their public health partners have the legal authority to quarantine specific individuals and animals to protect the public’s health. In addition, a CDC quarantine station may assure the isolation of specific individuals or animals that are reasonably believed to be carrying a communicable disease of public health significance. Through isolation, the infected persons or animals are separated from the population at large and their movement is restricted to prevent the microbial threat from spreading (DGMQ, 2004). Quarantine and isolation at national borders are non-medical components of the public health nontoolkit for limiting and containing the spread of microbial threats. Their utility varies, however, depending on the nature of the threat and the extent to which it has spread. 6 2/10/2010 PANDEMIC INFLUENZA PREPAREDNESS: COMMUNITY CONTROL AND PREVENTION • “Individual” Level • Individuals with flu-like illnesses should stay fluhome • Individuals with flu-like illnesses who cannot stay home should wear a face mask • Individuals with flu-like illnesses who cannot flustay home or wear a face mask should exhibit good “respiratory hygiene” (i.e. cover their coughs and sneezes) PANDEMIC INFLUENZA PREPAREDNESS: COMMUNITY CONTROL AND PREVENTION (CONTINUED) • “Community” Level • Targeted chemoprophylaxis of disease clusters • Quarantine of groups of exposed individuals • Cancellation of public gatherings and events even • Closure of facilities and public transportation • Community-wide “snow” days Community• Promotion of community-wide infection control measures community• Widespread community quarantine (cordon sanitaire) (cordon sanitaire) 7 2/10/2010 PANDEMIC INFLUENZA PREPAREDNESS: ANTIVIRAL DRUGS • Treatment of a suspected case of pandemic influenza: • Immediate isolation and administration of oseltamivir or zanamivir as early as possible (within 48 hours) • Prophylaxis of close contacts of a case of pandemic influenza: • Possible use of oseltamivir for health care provider contacts during influenza season, vaccination against seasonal influenza • Containment of disease clusters: • Before a pandemic is underway, possible targeted use of antiviral drugs to contain clusters of infection in “small, well-defined settings,” wellsuch as a military base 8 2/10/2010 NH1N1 Influenza Vaccines • Made in eggs using methods identical to those used to make annual influenza vaccine • Immunogenic, with one dose producing levels of antibody antibody likely to be protective in older children and adults adults • No adjuvant • Live attenuated and inactivated formulations available 9 2/10/2010 SWINE FLU, 1976 • January: “many” soldiers at Ft. Dix, N.J. developed flu-like illness; flulaboratory testing yielded a mix of H3N2 (A Victoria) and 4 cases (1 fatal) of H1N1 (Swine) Influenza • February:1 new case of H1N1 influenza and retrospective confirmation of February:1 Serosurve 8 additional earlier cases; Serosurvey suggests ~500 soldiers had been additional infected; Nearby civilian population: only H3N2 cases • October 1: Mass immunization began; >106 vaccinated in first 10 days • October 11:3 persons over age 70 died abruptly shortly after receiving 11:3 vaccine in Pittsburgh; Alleghany Co. and 9 states suspended immunizations • October 14: President Ford and his family vaccinated on national television SWINE FLU, 1976 (CONTINUED) • November 12: First case of Guillain-Barré GuillainSyndrome (GBS) in vaccine reported • December 16: Immunization program suspended after ~40x106 vaccinated estimate that GBS occurred in ~1 in 100,000 to 1 in 200,000 vaccinations 10 2/10/2010 Questions About NH1n1 Vaccine • What is its effectiveness? • Will it increase the risk of Guillain-Barre Syndrome? Guillain- Vaccine Efficacy Study Designs • Efficacy • Randomized, Placebo-Controlled Trials; Individuals Placebothe unit of randomization • Randomized, Placebo-Controlled Trials; PlaceboGroups/clusters the unit of randomization Clinical Trial Randomize Vaccine Placebo Vaccine Effectiveness Study Designs • Screening Method No Disease Disease No Disease Disease (Should be < 1.0) • Observational Cohort Studies • Prospective • Retrospective Rate or Risk Ratio = Ivac Iunvac • “Quasi-Cohort” Studies “Quasi• Case-Control Studies Case• Ecologic Studies Vaccine Efficacy = (1 - RR) x 100 Maximum Value = 100% No Minimum Value Effectiveness of NH1n1 Vaccine • Study Design: Case-Control Study Case• Case Definition? • Case Ascertainment • Control Selection Strategy(ies)? Strategy(ies)? • Ascertainment of Influenza Vaccine Exposure? • Possible Confounders to Measure? 11 2/10/2010 Risk of Guillain-barre Syndrome Guillainfollowing NH1n1 vaccine? • Study Design: Case Control Study • Case Definition? • Case Ascertainment? • Control Selection Strategy (ies?) (ies?) • Ascertainment of Influenza Vaccine Exposure? SUMMARY • The nH1N1 influenza pandemic is continuing and causing substantial morbidity and mortality worldwide • While most cases are mild and self-limited, a small selfproportion proportion of cases are severe and life-threatening, threatening especially especially in pregnant women, the massively obese, and individuals (children and adults) with underlying illnesses • Among the available prevention strategies, vaccination with the nH1N1 influenza vaccine is likely to be most effective. 12 ...
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